Dataset Information

Mitochondrial uncoupler carbonyl cyanide m-chlorophenylhydrazone induces vasorelaxation without involving K_ATP channel activation in smooth muscle cells of arteries.

ABSTRACT:

Background and purpose

The effects and mechanisms of chemical mitochondrial uncouplers on vascular function have never been identified. Here, we characterized the effects of the typical mitochondrial uncoupler carbonyl cyanide m-chlorophenylhydrazone (CCCP) on vascular function in rat mesenteric arteries and aorta and elucidated the potential mechanisms.

Experimental approach

Isometric tension of mesenteric artery and thoracic aorta was recorded by using a multiwire myograph system. Protein levels were measured by western blot analyses. Cytosolic [Ca²⁺ ]_i , mitochondrial ROS (mitoROS) and mitochondrial membrane potential of smooth muscle cells (A10) were measured by laser scanning confocal microscopy.

Key results

Acute treatment with CCCP relaxed phenylephrine (PE)- and high K⁺ (KPSS)-induced constriction of rat mesenteric arteries with intact and denuded endothelium. Pretreatment with CCCP prevented PE- and KPSS-induced constriction of rat mesenteric arteries with intact and denuded endothelium. Similarly, CCCP prevented PE- and KPSS-induced constriction of rat thoracic aorta. CCCP increased the cellular ADP/ATP ratio in vascular smooth muscle cells (A10) and activated AMPK in A10 cells and rat thoracic aorta tissues. CCCP-induced aorta relaxation was attenuated in AMPK ?1 knockout (-/-) mice. SERCA inhibitors thapsigargin and cyclopiazonic acid (CPA) but not the K_ATP channel blocker glibenclamide partially inhibited CCCP-induced vasorelaxation in endothelium-denuded rat mesenteric arteries. CCCP increased cytosolic [Ca²⁺ ]_i , mitoROS production and depolarized mitochondrial membrane potential in A10 cells. FCCP, the analogue of CCCP, had similar vasoactivity as CCCP in rat mesenteric arteries.

Conclusions and implications

CCCP induces vasorelaxation by a mechanism that does not involve K_ATP channel activation in smooth muscle cells of arteries.

SUBMITTER: Zhang YQ

PROVIDER: S-EPMC5056225 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature

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Mitochondrial uncoupler carbonyl cyanide m-chlorophenylhydrazone induces vasorelaxation without involving K<sub>ATP</sub> channel activation in smooth muscle cells of arteries.

Zhang Yan-Qiu YQ Shen Xin X Xiao Xiao-Lin XL Liu Ming-Yu MY Li Shan-Liang SL Yan Jie J Jin Jing J Gao Jin-Lai JL Zhen Chang-Lin CL Hu Nan N Zhang Xin-Zi XZ Tai Yu Y Zhang Liang-Shuan LS Bai Yun-Long YL Dong De-Li DL

British journal of pharmacology 20160909 21

<h4>Background and purpose</h4>The effects and mechanisms of chemical mitochondrial uncouplers on vascular function have never been identified. Here, we characterized the effects of the typical mitochondrial uncoupler carbonyl cyanide m-chlorophenylhydrazone (CCCP) on vascular function in rat mesenteric arteries and aorta and elucidated the potential mechanisms.<h4>Experimental approach</h4>Isometric tension of mesenteric artery and thoracic aorta was recorded by using a multiwire myograph syste ...[more]

PMID: 27534899

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